Low Cost Planetary Exploration: Surrey Lunar Minisatellite and Interplanetary Platform Missions

In order to meet the growing global requirement for affordable missions beyond Low Earth Orbit, two types of platform are under design at the Surrey Space Centre. The first platform is a derivative of Surrey’s UoSAT-12 minisatellite, launched in April 1999 and operating successfully in-orbit. The minisatellite has been modified to accommodate a propulsion system capable of delivering up to 1700 m/s delta-V, enabling it to support a wide range of very low cost missions to LaGrange points, Near-Earth Objects, and the Moon. A mission to the Moon - dubbed “MoonShine” - is proposed as the first demonstration of the modified minisatellite beyond LEO. The second platform - Surrey’s Interplanetary Platform - has been designed to support missions with delta-V requirements up to 3200 m/s, making it ideal for low cost missions to Mars and Venus, as well as Near Earth Objects (NEOs) and other interplanetary trajectories. Analysis has proved mission feasibility, identifying key challenges in both missions for developing cost-effective techniques for: spacecraft propulsion; navigation; autonomous operations; and a reliable safe mode strategy. To reduce mission risk, inherently failure resistant lunar and interplanetary trajectories are under study. In order to significantly reduce cost and increase reliability, both platforms can communicate with low-cost ground stations and exploit Surrey’s experience in autonomous operations. The lunar minisatellite can provide up to 70 kg payload margin in lunar orbit for a total mission cost US$16-25 M. The interplanetary platform can deliver 20 kg of scientific payload to Mars or Venus orbit for a mission cost US$25-50 M. Together, the platforms will enable regular flight of payloads to the Moon and interplanetary space at unprecedented low cost. This paper outlines key systems engineering issues for the proposed Lunar Minisatellite and Interplanetary Platform Missions, and describes the accommodation and performance offered to planetary payloads

Screening for Gynecologic Conditions With Pelvic Examination US Preventive Services Task Force Recommendation Statement

IMPORTANCE Many conditions that can affect women\u27s health are often evaluated through pelvic examination. Although the pelvic examination is a common part of the physical examination, it is unclear whether performing screening pelvic examinations in asymptomatic women has a significant effect on disease morbidity and mortality. OBJECTIVE To issue a new US Preventive Services Task Force(USPSTF) recommendation on screening for gynecologic conditions with pelvic examination for conditions other than cervical cancer, gonorrhea, and chlamydia, for which the USPSTF has already made specific recommendations. EVIDENCE REVIEW The USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women 18 years and older who are not at increased risk for any specific gynecologic condition. FINDINGS Overall, the USPSTF found inadequate evidence on screening pelvic examinations for the early detection and treatment of a range of gynecologic conditions in asymptomatic, nonpregnant adult women. CONCLUSIONS AND RECOMMENDATION The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women. (I statement) This statement does not apply to specific disorders for which the USPSTF already recommends screening (ie, screening for cervical cancer with a Papanicolaou smear, screening for gonorrhea and chlamydia)

Screening for Impaired Visual Acuity in Older Adults: US Preventive Services Task Force Recommendation Statement

DESCRIPTION: Update of the US Preventive Services Task Force (USPSTF) recommendation on screening for impaired visual acuity in older adults. METHODS: The USPSTF reviewed the evidence on screening for visual acuity impairment associated with uncorrected refractive error, cataracts, and age-related macular degeneration among adults 65 years or older in the primary care setting; the benefits and harms of screening; the accuracy of screening; and the benefits and harms of treatment of early vision impairment due to uncorrected refractive error, cataracts, and age-related macular degeneration. POPULATION: This recommendation applies to asymptomatic adults 65 years or older who do not present to their primary care clinician with vision problems. RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in older adults. (I statement)

Screening for Syphilis Infection in Nonpregnant Adults and Adolescents: US Preventive Services Task Force Recommendation Statement

Clinical Review & Education US Preventive Services Task Force | RECOMMENDATION STATEMENT Screening for Syphilis Infection in Nonpregnant Adults and Adolescents US Preventive Services Task Force Recommendation Statement US Preventive Services Task Force (USPSTF) Editorial page 2281 IMPORTANCE In 2014, 19 999 cases of syphilis were reported in the United States. Left untreated, syphilis can progress to late-stage disease in about 15% of persons who are infected. Late-stage syphilis can lead to development of inflammatory lesions throughout the body, which can lead to cardiovascular or organ dysfunction. Syphilis infection also increases the risk for acquiring or transmitting HIV infection. OBJECTIVE To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for syphilis infection in nonpregnant adults. Screening for syphilis in pregnant women was updated in a separate recommendation statement in 2009 (A recommendation). EVIDENCE REVIEW The USPSTF reviewed the evidence on screening for syphilis infection in asymptomatic, nonpregnant adults and adolescents, including patients coinfected with other sexually transmitted infections (such as HIV). Author Audio Interview at jama.com Related article page 2328 and JAMA Patient Page page 2367 CME Quiz at jamanetworkcme.com and CME Questions page 2342 Related articles at jamadermatology.com, jamaneurology.com, jamapediatrics.com FINDINGS The USPSTF found convincing evidence that screening for syphilis infection in asymptomatic, nonpregnant persons at increased risk for infection provides substantial benefit. Accurate screening tests are available to identify syphilis infection in populations at increased risk. Effective treatment with antibiotics can prevent progression to late-stage disease, with small associated harms, providing an overall substantial health benefit. CONCLUSIONS AND RECOMMENDATION The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection. (A recommendation) Authors/Group Information: The USPSTF members are listed at the end of the article. JAMA. 2016;315(21):2321-2327. doi:10.1001/jama.2016.5824 Corresponding Author: Kirsten Bibbins-Domingo, PhD, MD, MAS ([email protected]). T he US Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the bal- ance. The USPSTF does not consider the costs of providing a ser- vice in this assessment. The USPSTF recognizes that clinical decisions involve more con- siderations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clini- cal benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends screening for syphilis infection in per- sons who are at increased risk for infection. (A recommendation) (Figure 1) jama.com See the Clinical Considerations section later in this article for in- formation on risk factors for infection. Rationale Importance The number of cases of primary and secondary syphilis have been in- creasing since 2000. In 2014, 19 999 cases (6.3 cases per 100 000 persons)ofprimaryandsecondarysyphiliswerereportedintheUnited States. 1 Left untreated, syphilis can progress to late-stage disease in approximately 15% of persons who are infected. 2 Consequences of late-stage syphilis include development of inflammatory lesions throughout the body (eg, aortitis, gummatous lesions, and osteitis), which can lead to cardiovascular or organ dysfunction. Syphilis in- fection of the central nervous system (neurosyphilis) can occur at any stage of disease and can result in blindness, paresis, tabes dor- salis, and dementia. Syphilis infection also increases the risk for ac- quiring or transmitting HIV infection. The USPSTF addresses screening for syphilis in pregnant women in a separate recommendation statement. 3 (Reprinted) JAMA June 7, 2016 Volume 315, Number 21 Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jamanetwork.com/ by a University of California - Los Angeles User on 09/21/201

Best practices to maximize the use and reuse of quantitative and systems pharmacology models: recommendations from the United Kingdom quantitative and systems pharmacology network

The lack of standardization in the way that quantitative and systems pharmacology (QSP) models are developed, tested, and documented hinders their reproducibility, reusability, and expansion or reduction to alternative contexts. This in turn undermines the potential impact of QSP in academic, industrial, and regulatory frameworks. This article presents a minimum set of recommendations from the UK Quantitative and Systems Pharmacology Network (UK QSP Network) to guide QSP practitioners seeking to maximize their impact, and stakeholders considering the use of QSP models in their environment

Demonstration of surface electron rejection with interleaved germanium detectors for dark matter searches

The following article appeared in Applied Physics Letters 103.16 (2013): 164105 and may be found at http://scitation.aip.org/content/aip/journal/apl/100/26/10.1063/1.4729825The SuperCDMS experiment in the Soudan Underground Laboratory searches for dark matter with a 9-kg array of cryogenic germanium detectors. Symmetric sensors on opposite sides measure both charge and phonons from each particle interaction, providing excellent discrimination between electron and nuclear recoils, and between surface and interior events. Surface event rejection capabilities were tested with two 210 Pb sources producing ∼130 beta decays/hr. In ∼800 live hours, no events leaked into the 8–115 keV signal region, giving upper limit leakage fraction 1.7 × 10−5 at 90% C.L., corresponding to < 0.6 surface event background in the future 200-kg SuperCDMS SNOLAB experiment.This work is supported in part by the National Science Foundation (Grant Nos. AST-9978911, NSF-0847342, PHY-1102795,NSF-1151869, PHY-0542066, PHY-0503729, PHY-0503629, PHY-0503641, PHY-0504224, PHY-0705052,PHY-0801708, PHY-0801712, PHY-0802575, PHY-0847342, PHY-0855299, PHY-0855525, and PHY-1205898), by the Department of Energy (Contract Nos. DE-AC03-76SF00098, DE-FG02-92ER40701, DE-FG02-94ER40823,DE-FG03-90ER40569, DE-FG03-91ER40618, and DESC0004022),by NSERC Canada (Grant Nos. SAPIN 341314 and SAPPJ 386399), and by MULTIDARK CSD2009-00064 and FPA2012-34694. Fermilab is operated by Fermi Research Alliance, LLC under Contract No. De-AC02-07CH11359, while SLAC is operated under Contract No. DE-AC02-76SF00515 with the United States Department of Energy

Efficacy of Chlorhexidine Varnish for the Prevention of Adult Caries: A Randomized Trial

The Prevention of Adult Caries Study, an NIDCR-funded multicenter, double-blind, randomized clinical trial, enrolled 983 adults (aged 18-80 yrs) at high risk for developing caries (20 or more intact teeth and 2 or more lesions at screening) to test the efficacy of a chlorhexidine diacetate 10% weight per volume (w/v) dental coating (CHX). We excluded participants for whom the study treatment was contraindicated or whose health might affect outcomes or ability to complete the study. Participants were randomly assigned to receive either the CHX coating (n = 490) or a placebo control (n = 493). Coatings were applied weekly for 4 weeks and a fifth time 6 months later. The primary outcome (total net D1-2FS increment) was the sum of weighted counts of changes in tooth surface status over 13 months. We observed no significant difference between the two treatment arms in either the intention-to-treat or per-protocol analyses. Analysis of 3 protocol-specified secondary outcomes produced similar findings. This trial failed to find that 10% (w/v) chlorhexidine diacetate coating was superior to placebo coating for the prevention of new caries (Clinicaltrials.gov registration number NCT00357877)

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches